The present invention relates to novel compositions and methods for inhibiting immune responses associated with autoimmune diseases and allergic responses. In particular, it relates to vaccination with peptides from, for instance, the hypervariable region of MHC molecules encoded by alleles associated with disease.
A number of pathological responses involving unwanted immune responses are known. For instance, a number of allergic diseases, have been associated with particular MHC alleles or suspected of having an autoimmune component. Other deleterious T cell-mediated responses include the destruction of foreign cells that are purposely introduced into the body as grafts or transplants from allogeneic hosts. This process, known as "allograft rejection," involves the interaction of host T cells with foreign MHC molecules. Quite often, a broad range of MHC alleles are involved in the response of the host to an allograft.
Autoimmune disease is a particularly important class of deleterious immune response. In autoimmune diseases, self-tolerance is lost and the immune system attacks "self" tissue as if it were a foreign target. More than 30 autoimmune diseases are presently known; these include many which have received much public attention, including myasthenia gravis (MG) and multiple sclerosis (MS).
A crude approach to treating autoimmune disease and other immunopathologies is general immunosuppression. This has the obvious disadvantage of crippling the ability of the subject to respond to real foreign materials to which it needs to mount an immune response. Recent approaches to treating autoimmune disease have involved the use of peptides having an amino acid sequence encoded by a T-cell receptor V gene. The peptides have been proposed as vaccines for preventing, suppressing and treating immune related diseases (see, International Application No. WO 91/01133. Another approach involves the use of monoclonal antibodies against MHC gene products. The antibodies have been proposed for use in targeting cell bearing MHC molecules associated with particular diseases (see, EP Publication No. 68790).
These prior art methods fail to provide a simple self-mediated method for specifically eliminating immune responses restricted by glycoproteins encoded by MHC alleles associated with a variety of deleterious immune responses. Such methods can be used to prevent and/or suppress diseases, particularly those in which the antigen or allergen is not known.